The objectives of this proposal are: (1) Define the primary structural diversity among antibodies specific for the same antigen, relate structural information to defined idiotypic and antigen-binding properties, and assess molecular and genetic mechanisms responsible for generating antibody diversity; (2) characterize the primary structural diversity among the kappa light chain variable regions (VK) expressed by C58 and AKR murine strains and relate this information to define VK genetic markers which distinguish these VK's from those of other murine strains. The first objective will be addressed through amino acid sequence analysis of idiotypically defined and functionally characterized anti-group A streptococcal carbohydrate hybridoma antibodies. These antibodies will be representative of four levels of immunocompetence: antibodies elicited early in ontogeny (neonatal), adult primary antibodies, adult secondary antibodies and adult hyperimmune antibodies. These analyses will reveal the relative contributions to the functional antibody repertoire of germ line encoded variability versus somatically acquired variability; and the influence of somatic development and antigen stimulation in the generation of antibody diversity. The second objective, (2) above, will be addressed through sequence analysis of myeloma light chains derived from C.C58 and C.AKR mice which are congenic with the BALB/c myeloma-inducible strain and express the VK polymorphisms of C58 and AKR, respectively. These studies will identify structural correlates of the VK genetic markers and compare the diversity of C58 and AKR VK repertoires with that of other murine strains.